A number of investigators have suggested in small studies that rare alleles of the Harvey-ras protooncogene locus are associated with an increased risk of cancer. These alleles vary due to a variable number tandem repeat (VNTR) region on the 3' side of the gene. This region has transcriptional enhancer activity and so individuals with the rare VNTR alleles may overexpress the ras gene product. This may provide a mechanism to explain the observation of lung cancer susceptibility of these groups. The goal of this proposed research is to confirm that there is an association between the presence of a rare H-ras protooncogene allele and an increased risk of lung cancer. Restriction fragment length polymorphism (RFLP) analysis will be utilized to determine the nature of the H-ras alleles in normal tissues (lymphocytes) of 330 lung cancer patients and in 330 controls. This proposed study will be much larger, with considerable statistical power to stably estimate the magnitude of any observed association. Moreover, we will use a control group without other lung diseases which may be associated with rare alleles, allowing us to estimate the general population frequency of these rare alleles.